2-(p-alkoxyphenyl)-3-substituted indoles



United States Patent 0 ABSTRACT OF THE DISCLGSURE New 2-alkoxyphenyl 3substituted indoles, having sedative and tranquilizing action, of thetype R, I i lQ wherein R is selected from hydrogen, halogens, alkoxy,and alkyl, having 1 to 3 carbon atoms and R is an alkyl having from 1 to3 carbon atoms, and wherein the group are prepared by reacting aZ-(p-alkoxyphenyl) indole with an alkyl Grignard, then with ap-alkoXyphenyl-acetyl halide to obtain the corresponding p-alkoxybenzyl2-(palkoxyphenyl) indol-3-yl ketone (a) and reducing with lithiumhydride or lithium borohydride and if desired acid dehydrating to obtainthe compounds with groups (b), (c), and ((1) above.

This invention relates to novel compounds and is more particularlyconcerned with central nervous system depressantZ-(p-alkoxyphenyl)-3-substituted indoles (II, III, IV and V), and aprocess for the production thereof.

The novel products (II, III, IV and V) and a process for the productionthereof can be illustratively represented by the following sequence offormulae:

3,352,85fi Patented Nov. 14, 196'? wherein R is selected from the groupconsisting of hydrogen, fluorine, chlorine, bromine, iodine, alkoxyhaving from 1 to 3 carbon atoms, inclusive, i.e., methoxy, ethoxy,propoxy and isopropoxy, and alkyl having from 1 to 3 carbon atoms,inclusive, i.e., methyl, ethyl, propyl and isopropyl, and wherein R isan alkyl group having from 1 to 3 carbon atoms, inclusive.

The process of this invention comprises: Treating a2-(p-alkoxyphenyl)indole (I) with an alkyl Grignard reagent (e.g.,methylmagnesium bromide, ethylmagnesiurn iodide, butylmagnesium bromide,and the like) and thereupon with a p-alkoxyphenylacetyl chloride orbromide in which the alkoxy group has from 1 to 3 carbon atoms,inclusive, to obtain the corresponding p-alkoxybenzyl2-(p-alkoxyphenyl)indol-3-yl ketone (II); reducing compound II(A) withlithium aluminum hydride in an ether and decomposing the product to givethe corresponding Z-(p-allroxyphenyD-3-(p alkoxyphenethyl)indole (III);(B) with lithium borohydride in an ether and decomposing the product togive a-(p-alkoxybenzyl)-2-(p-alkoxyphenyl)indole-3methanol (IV) and2-(p-alkoxyphenyl)- 3-(p-alkoxystyryl)indole (V). Compounds of Formula Vare also obtained by dehydrating the compounds of Formula IV with acids.Compounds of Formula III can also be obtained by hydrogenating thecompounds of Formula V with hydrogen in the presence of a palladium orplatinum catalyst. Reduction of compound II with sodium borohydride inethanol yielded the starting compound of Formula I.

The compounds of Formulae II, III, IV and V of the present inventionhave a depressant activity on the cen tral nervous system and are thususeful for purposes of sedation and tranquilization in birds and mammalssuch as domestic pet animals, e.g., dogs and cats and farm animals,e.g., cattle, pigs, sheep, chickens, geese, ducks and the like. Sedationand tranquilization of animals is particularly important duringshipments of animals by truck, car, train, airplane, ship and so on,from one location to another to avoid agitation of the animal and thusprevent wounding and even death of the animals during transit. The abovecompounds II, III, IV and V are also useful for tranquilizing dogs whichhave lost their owners or undergo a change of ownership as these animals are Well-known to refuse water and food during such periods, oftenfor lengthy times, which can endanger their life and their health.

For cases where tranquilization is desired, oral and parenteral dosageforms may be used. The oral forms can be tablets, pills or liquids whilethe parenteral forms are LiAlHl LiBHt usually applied in the forms ofsolutions or suspensions. The starting materials of Formula I can beprepared by known methods, e.g., as shown in US. Patent 2,825,734 issuedMar. 4, 1958.

In carrying out the process of the present invention, the selected2(p-alkoxyphenyl)indole (I) is reacted with an alkylmagnesium halidereagent such as methylmagnesium bromide or methylmagnesium iodide underthe usual conditions of Grignard reactions, for example, using benzene,ether, cyclohexane, tetrahydrofuran, and the like assolvents andreacting slowly at about room temperature and finally at elevatedtemperature, usually at the reflux temperature of the reaction mixture.The thus-obtained reaction mixture is thereupon treated with ap-alkoxyphenylacetyl halide and the reaction mixture is refluxed for aperiod between a quarter of an hour to three hours. It is thendecomposed with water, or preferably aqueous mineral acid such asaqueous hydrochloric, hydrobromic, hydroiodic, sulfuric and other acids.The resulting suspension is filtered, the solids collected and purifiedby conventional means such as crystallization, recrystallization,trituration, extraction, chromatography and the like to give thecorresponding p-alkoxybenzyl 2-(p-alkoxyphenyl)indol-3-yl ketone (II).

The reduction of compound II can be carried out in different manners anddepending upon the type of reducing agent and solvent used, differentindole compounds are obtained:

(A) The reduction of p-alkoxybenzyl 2-(p-alkoxyphenyl)indol-3-yl ketone(II) with lithium aluminum hydride.-The reduction of p-alkoxybenzyl2-(p-alkoxyphenyl)indol-S-yl ketone with lithium aluminum hydride iscarried out in an ether, such as tetra-hydrofuran, diethyl ether,dibutyl ether and the like, preferably in a nitrogen atmosphere, at thereflux temperature of the mixture. The reaction time is usually betweenone hour and 48 hours. At the termination of the reaction, the mixtureis decomposed, for example, by the addition of water and an alkali metalhydroxide, such as aqueous sodium hydroxide, aqueous potassiumhydroxide, aqueous lithium hydroxide and the like. The obtainedsuspension is filtered and the thus-produced solids containing thedesired prodnot, a 3 (p-alkoxyphenethyl)-2-(p-alkoxyphenyl)indole (III)is purified by conventional procedures such as. re-

crystallization, chromatography and combinations thereof.

(B) The reduction p-alkoxyb'enzyl Z-(p-alkoxyphenyl)irzdol-3-ylket0ne-(ll) with lithium b0r0hydride.- The lithiunrborohydride reductionof p-alkoxybenzyl 2- (p-alkoxy henyl)indol-3-yl ketone is carried out inan ether such as tetrahydrofuran, diethyl ether, dibutyl ether or thelike, at a temperature between and 50 C., usually at room temperature.The reaction time is between one to- 48 hours. Room temperature and areaction time between to hours is a preferred embodiment of thisinvention. After the reaction is completed, the reaction mixture isdecomposed by the addition of water and an alkali metal hydroxide, suchas aqueous sodium hydroxide, potassium hydroxide, lithium hydroxide andthe like. The resulting suspension is filtered, the filtrate isevaporated and the residue is purified by conventional means such ascrystallization, recrystallization, extraction,

chromatography and the like, to give two products, name- 1y,a-(p-alkoxybenzyl) 2 (palkoxyphenyl)indole-3- methanol (IV) and2-(p-alkoxyphenyl) 3 (p-alkoxystyryl)indole (V) which are separated,usually by using the differential solubilities of these products inorganic solvents.

(C) The reduction of p-alkoxybenzyl 2.- (p-alkoxy- Alternatively, a3-(p-alkoxyphenetl1yl) 2 (p-alkoxyphenyl)indole (III) can also, beobtained by hydrogenating a 2-(p-alkoxyphenyl)-3-(p-alkoxystyryl)indole(V) in the presence of a palladium catalyst or a platinum catalyst, andan inert solvent such as methanol, ethanol, dioxane, ethyl acetate, andthe like.

Alternatively, a Z-(p-alkoxyphenyl)-3-(p-alkoxystyryl) indole (V) can beobtained by dehydration of an a-(palkoxybenzyl) 2(p-alkoxyphenyl)indole-3-methanol (IV). The reaction is advantageouslyperformed in an inert solvent such as chloroform, carbon tetrachloride,methylene chloride, and the like, in the presence of a mineral acid suchas hydrogen chloride, hydrogen bromide, hydrogen iodide or sulfuric aciddiluted in an ether such as diethyl ether or tetrahydrofuran.

The following examples are illustrative of the process and products ofthe present invention, but are not to be construed as limiting:

EXAMPLE 1 p-Mezhoxybenzyl 2-(p-I'neth0xyphenyl)ind0l-3-yl ketone Asuspension of 75.2 g. (0.337 mole) of 2-(p-methoxyphenyl)indole in 2 l.of benzene was heated to boiling and then cooled to a temperature of 40to 50 C. To this mixture was added 114 ml. of a 3 M ether solution ofmethylmagnesium bromide (0.342 mole). The addition was carried outdrop-wise over a period of 30 minutes. The resulting solution wasrefluxed for a period of 1.5 hours. It was then cooled to roomtemperature and 62 g. (0.337 mole) of p-methoxyphenylacetyl chloride[see I. Am. Chem. Soc. 76, 1883 (1954)] was added over a period of 20minutes. The mixture was refluxed for 1.5 hours and allowed to stand for18 hours. It was then decomposed by the addition of a solution of ml. ofcon centrated hydrochloric acid in 350 ml. of water. A suspensionresulted, which was filtered, the solids washed.

with benzene, then with water, providing 13.1 g. of a product melting at196 to 206 C. This product was crystallized from chloroform to give 4 g.of recovered starting material, 2-(p-methoxyphenyl)indole. The filtrateobtained above was separated into two layers. The organic layer waswashed with water, then with a saturated sodium chloride solution, thendried by passing it through anyhydrous sodium sulfate. The driedsolution was evaporated, providing a colored solid which was trituratedwith ether and the mixture was filtered. The resulting solid wascrystallized from ethanol, giving p-methoxybenzyl2-(pmethoxyphenyl)indol-3-yl ketone in two crops, 31.5 g. melting at tol71.5 C. and 14 g. melting at 168 to 171 C., a total yield of. 36percent. An analytical sample of this compound obtained byrecrystallization from ethanol melted at 170.5 to 171.5 C.

Analysis.Calcd. for C H NO C, 77.60; H, 5.70; N, 3.77. Found: C, 77.28;H, 5.92; N, 3.88.

EXAMPLE 2 p-Ethoxybenzyl-Z- (p-ethoxyphenyl -5-flu0r0ind0l-3-yl ketoneIn the manner given in Example 1, 2-(p-ethoxyphenyl)- S-fluoroindole wastreated first with methylmagnesium bromide and then withp-ethoxyphenylacetyl chloride to give p-ethoxybenzyl2-(p-ethoxyphenyl)-5-fluoroindol-3- yl ketone.

EXAMPLE 3 p-Methoxybcnzyl 2- (p-methoxyphenyl -7-chl0r0ind0l- 3-ylketone In the manner given in Example 1,Z-(p-methoxyphenyl)-7-chloroindole was treated first with methylmanesium bromide and then with p-methoxyphenylacetyl chloride to givep-methoxybenzyl 2-(p-methoxyphenyl) 7-chloroindol-3-yl ketone.

EXAMPLE 4 p-Ethoxybenzyl 2- p-eth oxy phenyl -7 -brm0incl0 [-3 -y[ketone In the manner given in Example 1, 2-(p-ethoxyphenyl)-7-bromoindole was treated first with methylmagnesium bromide and thenwith p-ethoxyphenylacetyl chloride to give pethoxybenzyl2-(p-ethoxyphenyl)-7-bromoindol-3- yl ketone.

EXAMPLE 5 p-Methoxybenzyl Z-(p-ethoxyphenyl)-7-i0d0ind0l-3-yl ketone Inthe manner given in Example 1, 2- (p-methoxyphenyl)-7-iodoindole wastreated first with methylmagnesium bromide and then withp-methoxyphenylacetyl chloride to give p-metho-xybenzyl2-(p-methoxyphenyl)- 7-iodoindol-3-y1 ketone.

EXAMPLE 6 p-Methoxybenzyl Z-(p-methoxyphenyl)-4-methoxyind0l- 3-ylketone In the manner given in Example 1,2-(p-rnethoxyphenyl)-4-methoxyindole was treated first with methyLmagnesium bromide and then with p-methoxyphenylacetyl chloride to givep-methoxybenzyl 2-(p-methoxyphenyl)-4-methoxyindol-3-yl ketone.

EXAMPLE 7 p-Propoxybenzyl 2- (p-propoxyph enyl) -6-eth0xyind0l-3-ylketone In the manner given in Example 1, Z-(p-propoxyphenyl)-6-ethoxyindole was treated first with methylmagnesium bromide and thenwith p-propoxyphenylacetyl chloride to give p-propoxybenzyl2-(p-pr0poxyphenyD-6- ethoxyindol-3-yl ketone.

EXAMPLE 8 p-Ethoxybenzyl 2- (p-ethoxyphenyl) -5-pr0poxyind0l-3-yl ketoneIn the manner given in Example 1, 2-(p-ethoxyphenyl)- 5-propoxyindolewas treated first with methylmagnesium bromide and then withp-ethoxyphenylacetyl chloride to give p-et-hoxybenzyl2-(p-ethoxyphenyl)-5-propoxyindol- 3-yl ketone.

EXAMPLE 9 p-Methoxybenzyl 2- (p -m ethoxyph enyl) -4-m ethy lindol-S- ylketone In the manner given in Example 1,Z-(p-methoxyphenyl)-4-methylindole was treated first withmethylmagnesiurn bromide and then with p-methoxyphenylacetyl chloride togive p-met-hoxybenzyl 2-(p-methoxyp-henyl)- 4-methylindol-3-yl ketone.

EXAMPLE 10 p-Methoxybenzyl 2- (p-m ethoxyphenyl) -5-pr0py lind0l-3- ylketone In the manner given in Example 1, 2-(p-rnethoxyphenyl)-5-propylindole was treated first with methylmagnesium bromideand then with p-methoxyphenylacetyl chloride to give p-methoxybenzyl2-(p-methoxyphenyl)- 5-propylindol-3-yl ketone.

EXAMPLE ll p-Methoxybenzyl Z-(p-methoxyphenyl) -5-ethylind0l-3-yl ketoneIn the manner given in Example 1, 2-(p-methoxyphenyD-S-ethylindole wastreated first with methylmagnesium bromide and then withp-methoxyphenylacetyl chloride to give p-methoxybenzylZ-(p-rnethoxyphenyD- 5-ethylind0l-3-yl ketone.

6 EXAMPLE 12 2- (p-ethoxyphenyl) -6-methylinaol-3-yl ketonep-Ethoxybenzyl In the manner given in Example 1, 2-(p-ethoxyphenyl)-6-methylindole was treated first with methylmagnesium bromide and thenwith p-ethoxyphenylacetyl chloride to give p-ethoxybenzyl2-(p-ethoxyphenyl)-6-methylindol-3- yl ketone.

EXAMPLE 13 p-Methoxybenzyl 2- (p-m ethoxyphenyl) -6-chl0r0ind0l-3- ylketone In the manner given in Example 1,2-(p-methoxyphenyl)-6-.ohloroindole was treated first with methylmagnesium bromide and then with p-methoxyphenylacetyl chloride to givep-methoxybenzyl 2-(p-methoxyphenyl)- 6-chloroindol-3-yl ketone.

EXAMPLE 14 p-Methoxybenzyl 2- (p methoxyphenyl) -7-m ethoxyindol- 3-ylketone In the manner given in Example 1,Z-(p-methoxyphenyl)-7-methoxyindole was treated first withmethylmagnesium bromide and then with p-methoxyphenylacetyl chloride togive p-methoxybenzyl 2-(p-methoxyphenyl)-7-methoxyindol-3-yl ketone.

EXAMPLE 15 p-Methoxybenzyl 2- (p -methoxyphenyl) -4-i0 d0indol-3-ylketone In the manner given in Example 1, 2-(p-methoxyphenyl)-4iodoindolewas treated first with methylmagnesium bromide and then withp-methoxyphenylacetyl chloride to give p-methoxybenzylZ-(p-methoxyphenyD- 4-iodoindol-3-yl ketone.

In the same manner given in Example 1, other palkoxy-benzyl2-(p-alkoxyphenyl)indo1-3-yl ketones are prepared by reacting a selected2-(p-alkoxyphenyl)indole first with methylmagnesium halide and then witha selected p-alkoxyphenylacetyl halide. Representative palkoxybenzyl2-(p-alkoxyphenyl)indol-S-yl ketones thus obtained include:

EXAMPLE 16 3-(p-m'eth0xyphenethyl) -2- (p-methoxyphenyl) indole Asolution of 37.1 g. (0.1 mole) of p-methoxybenzyl 2-(p-methoxyphenyl)indol-3-yl ketone in 500 ml. of tetrahydrofuran wasadded to a solution of 37.1 g. of lithium aluminum hydride in 2500 ml.of tetrahyd-rofuran during a period of 20 minutes in a nitrogenatmosphere. The thus-obtained mixture was refluxed while stirring for aperiod of 17 hours. It was then cooled in ice and decomposed bysuccessive addition of 37 ml. of water, 37 ml. of aqueous 15 percentsodium hydroxide solution and 111 ml. of water. A suspension was thusobtained, which was filtered, the solids washed with tetrahydrofuran,the washings combined with the filtrate and then evaporated to give 37.8g. of a brown oil as a residue. This residue was dissolved in 20 ml. ofmethylene chloride and 50 ml. of percent acetone, 85 percent SkellysolveB hexanes. This solution was chromatographed over 1134 g. of Florisil(anhydrousmagnesium silicate). The Florisil-containing column was elutedwith a mixture of 15 percent acetone, 85 percent Skellysolve B hexanes;350 ml. fractions of eluate were collected. Fractions 11 through 17 werecombined and evaporated to give 265 g. of an oil. This oil wascrystallized from ether-petroleum ether to give 15.26 g. (43 percent) of3-(methoxyphenethyl)-2-(p-methoxyphenyl)indole of melting point 80 to 82C. After additional crystallization from Skellysolve B hexane-ether,3-(p-methoxyphenethyl)-2-(p-methoxyphenyl)indole of melting point78.5,to 80 C. was ob tained which remained unchanged after additionalrecrystallization.

Analysis.-Calcd. for C H NO C, 80.64; H, 6.49; N, 3.92. Found: C, 80.23;H, 6.01; N, 3.51.

A reduction was undertaken with 3.71 g. of p-methoxybenzylZ-(p-methoxyphenyl)indol-S-yl ketone in 250 ml. of ethanol in thepresence. of 3.7 g. of sodium horohydride. The mixture was stirred atroom temperature overnight. The resulting solution was evaporated todryness, decomposed with 100 ml. of water and the solid filtered andWashed with water. Crystalliaztion from ethanol gave the startingmaterial of Example 1, 2-methoxyphenyl-indole of melting point 228 to229 C.

EXAMPLE 17 3- (p-ethoxyp-henethyl) -2- (p-ethoxyphenyl) -5-flu0r0-indole In the manner given in Example 16, p-ethoxybenzyl 2-(p-ethoxyphenyl)-5-fluorindol-3-yl ketone was reduced with lithiumaluminum hydride intetrahydrofuran and the resulting mixture wasdecomposed with water and aqueous sodium hydroxide to give3-(p-ethoxyphenethyl) -2- (p-ethoxyphenyl) -5-fluoroindole.

EXAMPLE l8 3 (p methoxyphenethyl) 2 (p methoxyphenyl) 7- chloroindole Inthe manner given in Example 16, p-methoxybenzyl2-(p-methoxyphenyl)-7-chloroindol-3-yl ketone was reduced with lithiumaluminum hydride in tetrahydrofuran and the resulting mixture wasdecomposed with water and aqueous sodium hydroxide to give3-(p-methoxyphenethyl) -2- (p-methoxyphenyl) -7-chloroindole.

EXAMPLE 19 3- (p-etlzoxyphenethyl) -2-(p-ethoxypherzyl) -7- bromoindoleIn the manner given in Example 16, p-ethoxybenzyl 2-(p-ethoxyphenyl)-7-bromoindol-3-yl ketone was reduced with lithium aluminum hydride intetrahydroturan and the resulting mixture was decomposed with water andaqueous sodium hydroxide to give 3-(p-ethoxyphenethyD- 2-p-ethoxyphenyl) -7-bromoindole.

EXAMPLE 20 3-(p-methoxyphenethyl) -2- (p-methoxyphenyl) 7- iodoindole Inthe manner given in Example 16, p-methoxybenzyl2-(p-methoxyphenyl)-7-iodoindol-3-yl ketone was reduced with lithiumaluminum hydride in tetrahydrofuran and the resulting mixture wasdecomposed with water and aqueous sodium hydroxide to give3-(p-ethoxyphenethyl)- ethyl) -2- (p-methoxyphenyl) -7-iodoindole.

8 EXAMPLE 21 3-(p-methoxyphenethyl) -2- (p-methoxyphenyl)-4-methoxyindole In the manner given in Example 16, p-methoxybenzylZ-(p-methoxyphenyl)-4-methoxyindol-3-yl ketone was reduced with lithiumaluminum hydride in tetrahydrofuran and the resulting mixture wasdecomposed with water and aqueous sodium hydroxide to giveS-(p-methoxyphenethyl) -2- (p-methoxyphenyl) -4-methoxyindole.

EXAMPLE 22 3 p-propoxyphenethyl -2( p-propoxyphenyl -6- ethoxyindole Inthe manner given in Example 16, p-propoxyhenzylZ-(p-propoxyphenyl)-6-ethoxyindol-3-yl ketone was reduced with lithiumaluminum hydride in tetrahydrofurau and the resulting mixture wasdecomposed with water and aqueous sodium hydroxide to give3-.(p-propoxyphenethyD- 2-(p-propoxypheny1) -6-ethoxyindole.

EXAMPLE 23 3-(ethoxyphenvethyl) -2-(p-ethoxyphenyl) -5-propoxyindole Inthe manner given in Example 16, p-ethoxybenzyl2-(p-ethoxyphenyl-S-propoxyindol-3-yl ketone was reduced with lithiumaluminum hydride in tetrahydrofuran and the resulting mixture wasdecomposed with water and aqueous sodium hydroxide to give3-(p-ethoxyphenethyl)-2-(p-ethoxyphenyl)-5-propoxyindole.

EXAMPLE 24 3-(p-methoxyphenethyl)-2-(p-methoxyphenyl) -4- methylindoleIn the manner given in Example 16, p-methoxybenzylZ-(p-methoxyphenyl)-4-methylindol-3-yl ketone was reduced with lithiumaluminum hydride in tetrahydrofuran and the resulting mixture wasdecomposed with Water and aqueous sodium hydroxide to give3-(p-methoxyphenethyl) -2- (p-methoxyphenyl) -4-methylindole.

EXAMPLE 25 3-(p-methoxyphenethyl) -2-(p-methoxyph-enyD-S- propylindoleIn the manner given in Example 16, p-methoxybenzyl2-(p-methoxyphenyl)-5-propylindol-3-yl ketone was reduced with lithiumaluminum hydride in tetrahydrofuran and the resulting mixture wasdecomposed with water and aqueous sodium hydroxide to give3-(p-methoxyphenethyl) -2- (p-methoxyphenyl) -5-ethylindole.

EXAMPLE 26 3-(p-meth0xyphenethyl) -2-(p-methoxyphenyl) -5- ethylz'ndoleIn the manner given in Example 16, p-methoxyhenzyl Z-(p-ethoxyphenyl) 5methylindol-3-yl ketone was reduced with lithium aluminum hydride intetrahydrofuran and the resulting mixture was decomposed with water andaqueous sodium hydroxide to give 3-(p-rnethoxyphenethyl -2-p-methoxyphenyl -5-ethylindole.

EXAMPLE 27 3-(p-eth0'xyphenethyl)-2-(p-eth0xyphenyl) -6- methylina'ole 9EXAMPLE 2s 3-(p-meth0xyphenethyl) -2-(pmeth0xyphenyl) -6- chloroindoleIn the manner given in Example 16, p-methoxybenzyl Z-(p-methoxy)-6-chloroindol-3-yl ketone was reduced with lithium aluminum hydride intetrahydrofuran and the resulting mixture was decomposed with water andaqueous sodium hydroxide to give 3-(p-methoxyphenethyl)- 2-(p-methoxyphenyl) -6 chloroindole.

EXAMPLE 29 3-(p-methoxyphenethyl) -2- (p-methoxyphenyl) -7-methoxyindole In the manner given in Example 16, p-methoxybenzyl2-(p-methoxyphenyl)-7-methoxyindol-3-yl ketone was reduced with lithiumaluminum hydride in tetrahydrofuran and the resulting mixture wasdecomposed with water and aqueous sodium hydroxide to give3-(p-methoxyphenethyl -2- (p-methoxyphenyl) -7-methoxyindole.

EMMPLE 30 3- (p-methoxyphenethyl) -2-(p-methmcyphenyl) -4- iodoindole Inthe manner given in Example 16, p-methoxybenzylZ-(p-methoxyphenyl)-4-iodoindol-3-yl ketone was reduced with lithiumaluminum hydride in tetrahydrofuran and the resulting mixture wasdecomposed with water and aqueous sodium hydroxide to give3-(p-methoxyphenethyl) -2-(p-metl1oxyphenyl) -4-iodoindole.

In the manner given in Example 16, other3-(p-alkoxyphenethyl)-2-(p-alkoxyphenyl)indoles can be prepared byreducing selected p-alkoxybenzyl 2 (p alkoxyphenyl) indol-3-yl ketoneswith lithium aluminum hydride in tetrahydrofuran and decomposing theresulting mixture with aqueous sodium hydroxide. Representative3-(p-alkoxyphenethyl)-2-(p-alkoxyphenyl)indoles thus prepared include: 3(p-ethoxyphenethyl) 2 (p-ethoxyphenyl 6- chloroindole;3-(p-methoxyphenethyl) 2 (p methoxyphenyl) 6 fiuoroindole; 3 (ppropoxyphenethyl)-2- (p-propoxyphenyl) 4 bromoindole; 3 (pmethoxyphenethyl) 2 (p methoxyphenyl) 6 propoxyindole; 3 (pethoxyphenethyl) 2 (p ethoxyphenyl) 7- methylindole; 3 (ppropoxyphenethyl) 2 (p propoxyphenyl) 7 ethoxyindole: 3 (ppropoxyphenethyl) 2 (p propoxyphenyl) methylindole; 3(pmethoxyphenethyl) 2 (p methoxyphenyl) 5 bromoindole; 3 (pethoxyphenethyl) 2 -(p ethoxyphenyl) indole; 3-(p-methoxyphenethyl) 2(p-methoxyphenyD- 6-indoindole; and the like.

EXAMPLE 31 a-(p-methoxybenzyl) 2 (p methuxyphenyl) indole 3- methanoland Z-(p-methoxyphenyl) -3 (p methoxystyryl) indole A solution of 20.2g. (0.0545 mole) of p-methoxybenzyl Z-(p-methoxyphenyl)indol-3-yl ketonein 270 ml. of tetrahydrofuran was added to a suspension of 20.2 g. oflithium borohydride in 220 ml. of tetrahydrofuran. The mixture was thenstirred at room temperature (about 25 C.) for a period of 18 hours. ItWas then cooled in ice and decomposed by successive addition of 21 ml.of water, 21 ml. of aqueous 15 percent sodium hydroxide solution and 63ml. of water. After stirring the mixture for about 30 minutes, theresulting suspension was filtered and the filtrate was evaporated todryness in vacuo. The thus-obtained residue Was stirred with l l. ofwater and 700 ml. of ether. The layers were separated and the aqueouslayer was extracted with three l00-'nl. fractions of methylene chloride.The ether layer and the methylene chloride extracts were combined,washed with water, then with saturated aqueous sodium chloride andfinally dried by passage through anhydrous sodium sulfate. The driedsolution was evaporated to give a residue which was crystallized frommethanol to give 11.7 g. ofa-(p-methoxybenzyl)-2-(p-methoxyphenyl)indole-3-methanol of meltingpoint 143 to 144 C. This material was once more recrystallized frommethanol to give 4.6 g. of pure a-(p-methoxybenzyl)-2(p-methoxyphenyl)indole 3 methanol having the same melting point of 143to 144 C.

Analysis.-Calcd. for C I-1 N0 2 C, 77.19; H, 6.21; N, 3.75. Found: C,77.39; H, 6.31; N, 3.72.

The methanolic filtrates from above were combined and evaporated todryness. The residue was dissolved in methylene chloride andchromatographed over 650 g. of Florisil (anhydrous magnesium silicate),eluting with 2 l. of methylene chloride and collecting fractions of 200ml. Fractions 5 through 9 were combined and evaporated, and the solidwas crystallized from methanol to give 8.34 g. (43 percent) of2-(p-rnethoxyphenyl) 3 (p methoxystyryl)indole of melting point 142 to143 C.

Analysis.Calcd. for C I-1 N0 2 C, 81.10; H, 5.96; N, 3.94. Found: C,81.08; H, 5.93; N, 3.63.

EXAMPLE 32 a-(p-Ethoxybenzyl) -2-(p-eth0xyphenyl) 5 fluoroindole-3-methanol and Z-(p-ethoxyphenyl)-3-(p-ethoxystyryl)- 5-flu0r0ind0le Inthe manner given in Example 31, p-ethoxybenzyl-Z-(p-ethoxyphenyl)-5-fiuoroindol-3-yl ketone was reduced with lithiumborohydride in tetrahydrofuran and subsequently decomposed with diluteaqueous sodium hydroxide solution to givea-(p-ethoxybenzyl)-2(p-ethoxyphenyl)-5-fluoroindole-3-methanol and2-(p-ethoxyphenyl)-3-p ethoxystyryl) 5 fluoroindole, which wereseparated as in Example 31.

EXAMPLE 33 oc- (p-Methoxybenzyl)-2-(p-meth0xyphenyl) 7chloroind0le-3-methan0l and 2-(p-melh0xyphenyD-3 (p methovcystyryl)-7-chl0r0ind0le In the manner given in Example 31, p-methoxybenzyl2-(p-meth0xyphenyl)7-chl0rOindOl-3-yl ketone was reduced with lithiumborohydride in tetrahydrofuran and subsequently decomposed with diluteaqueous sodium hydroxide solution to giveu-(p-methoxybenzyl)-2-(p-methoxyphenyl)-7-chloroindole-3 methanol and 2(p methoxyphenyl) -3- (p-methoxystyryl -7-chloroindole, which wereseparated as in Example 31.

EXAMPLE 34 cc- (p-Elhoxybenzyl) -2- (p-ethoxyphenyl) -7 bromoznaole- 3-methanol and 2- (p-ethoxyph enyl -3 (p-e thoxystyryl 7-br0m0ind0le Inthe manner given in Example 31, p-ethoxybenzyl2-(p-ethoxyphenyl)-7-bromoindol 3 yl ketone was reduced with lithiumborohydride in tetrahydrofuran and subsequently decomposed with diluteaqueous sodium hydroxide solution to givea-(p-ethoxybenzyl)-2(p-ethoxyphenyl)-7-bromoindole-3-methanol and2-(p-ethoxyphenyl)-3-(p-ethoxystyryl)-7-bromoindole, which wereseparated as in Example 31.

EXAMPLE 35 a-(p-MethoxybenzyD-Z-(p methoxyphenyl) 7iodoind0le-3-methanol and 2-(p-methoxyphenyl)-3 (p methovcystyryl)-7-i0doz'nd0le phenyl)-3(p-methoxystyryl) 7 iodoindole, which wereseparated as inExample 31.

1 1 EXAMPLE 36 a-(p-Methoxybenzyl)-2-(p-meth0xyphenyl)-4methoxyindle-3-mcflzan0l and 2-(pmeth0xyphenyl) -3-(pmethoxystyryl)-4-meth0xyind0le In the manner given in Example 31,p-methoxybenzyl 2-(p-methoxyphenyl)-4-methoxyindol 3 yl ketone wasreduced with lithium borohydride in tetrahydrofuran and subsequentlydecomposed with dilute aqueous sodium hydroxide solution to givea-(p-mBthoxybenzyD-Z-(p-methoxyphenyl)-4-methoxyindole-3-methanol and2-(p methoxyphenyl)-3 (p methoxystyryl) 4 methoxyindole, which wereseparated as in Example 31.

EXAMPLE 37 ot-(p-Propoxybenzyl)-2-(p-pr0p0xyphenyl) 6ethoxyindole-.i-metlzanol and 2-(p-pr0p0xyphenyl)-3 (p propoxystylyl)-6-etlz0xyindole In the manner given in Example 31, p-propoxybenzylZ-(P-pmpoxyphenyl)-6-ethoxyindol 3 yl ketone was reduced with lithiumborohydride in tetrahydrofuran and subsequently decomposed with diluteaqueous sodium hydroxide solution to givec-(p-propoxybenzyl)-2-(p-propoxyphenyl)-6-ethoxyindole-3 methanol and 2(p propoxyphenyl)-3-(p-propoxystyryl)-6 ethoxyindole, which wereseparated as in Example 31.

EXAMPLE 38 a-(p-Ethoxybenzyl)2-(p ethoxyphenyl) pro-poxyim,

dole-3421 ethanol and 2- (p-etl zoxyphenyl) -3- (p-eth0xyslyryl)-5-pr0p0xyind0le In the manner given in Example 31, p-ethoxybenzyl2-(p-ethoxyphenyl)-5-propoxyindol 3 yl ketone was reduced with lithiumborohydride in tetrahydrofuran and subsequently decomposed with diluteaqueous sodium hydroxide solution give :x-(p-ethoxybenzyD-2 (pethoxyphenyl)-5-propoxyindole-3-methanol and 2 (pethoxyphenyl)3-(p-ethoxystyryl)-5-propoxyindole, which were separated asin Example 31.

EXAMPLE 39 a-(p-Methoxybenzyl)-2-(p-methoxyphenyD-4metlzylindole-.i-methanol and 2-(p-methoxyphenyl)3-(p-methoxystyryl)-4-methylind0le In the manner given in Example 31, p-methoxybenzyl2-(p-methoxyphenyl)-4-methylindol-3-yl ketone was reduced with lithiumborohydride in tetrahydrofuran and subsequently decomposed with diluteaqueous sodium hydroxide solution to giveot-(p-methoxybenzyl)-2-(p-methoxyphenyl)-4-methylindole-3-methanol and 2(p methoxyphenyl -3 (p-methoxystyryl) -4-methylindole, which wereseparated as in Example 31.

EXAMPLE 4O a-(p-Methoxybenzyl)-2-(p-methoxyphenyl) 5propylind0le-3-mcthan0l and 2-(p-methoxyphenyl)-3-(p-metlzoxystyryl)5-pr0pylind0lc In the manner given in Example 31, p-methoxybenzyl2-(p-methoxyphenyl)-5-propylindol-3-yl ketone was reduced with lithiumborohydride in tetrahydrofuran and subsequently decomposed with diluteaqueous sodium hydroxide to give a-(p-methoxybenZyD-2(pmethoxybenzyl)-5-propylindole-3-methanol and 2 (pmethoxyphenyl)-3-(p-methoxystyryl) 5-propylindole, which were separatedas in Example 31.

EXAMPLE 41 a-(p-Methoxybenzyl)-2-(p-metlzoxyphenyl) 5ethylirzd0le-3-methanol and Z-(p-methoxyphenyl) 3(p-methaxystyryl)-5-ethylina'ole In the manner given in Example 31,p-methoxybenzyl Z-(p-methoxyphenyl)-5-ethylindol 3 yl ketone was reducedwith lithium borohydride in tetrahydrofurau and subsequently decomposedwith dilute aqueous sodium hydroxide solution to givea-(p-methoxybenzyl)-2-(p-methoxyphenyl)-5-ethylindole-3-methanol and2-(p-methoxyphenyl)-3-(p-methoxystyryl)-5-ethylindole, which wereseparated as in Example 31.

EXAMPLE 42 a-(p-Ethoxybenzyl)-2-(p-ethoxyphcnyl)-6 mcthylindolc-3-methan0l and Z-(p-ethoxyphenyl)-3-(p-eth0xystyryl)- 6-methylind0le Inthe manner given in Example 31, p-ethoxybenzyl2-(p-ethoxyphenyl)-6-methylindol 3 yl ketone was reduced with lithiumborohydride in tetrahydrofurau and subsequently decomposed with diluteaqueous sodium hydroxide solution to givea-(p-ethoxybenzyl)-2-(p-ethoxyphenyl)-6-methylindole 3 methanol and 2 (pethoxyphenyl)3-(p-ethoxystyry1) 6 methylindole which were separated asin Example 31.

EMMPLE 43 zx-(p-Methoxybenzyl)-2-(p-mcthoayphenyl) 6chloroind0le-3-methan0l andZ-(p-methoxyphenyl)-3-(p-methoxystyryl)-6-chl0r0indole In the mannergiven in Example 31, p-methoxybenzyl2-(p-methoxypheny-l)-6-chloroindol-3-y1 ketone was reduced with lithiumborohydride in tetrahydrofuran and subsequently decomposed with diluteaqueous sodium hydroxide solution to give a-(p-methoxybenzyl) 2-(p-methoxyphenyl) -6-chloroindole-3 methanol and 2 (p methoxyphenyl -3(p-methoxystyryl -6-chloroindole, which were separated as in Example 31.

EXAMPLE 44 a- (p-Methoxybenzyl) -2- (p-mcthoxyphenyl) -7methoxyind0le-3-methan0l and 2- (p-methoxyphenyl) -3- J-methoxystyryl)-7-meth0xyind0le In the manner given in Example 31, p-methoxybenzyl2-(p-methoxyphenyl)-7-meth0xyindol-3-yl ketone was reduced with lithiumborohydride in tetrahydrofuran and subsequently decomposed with diluteaqueous sodium hydroxide solution to givea-(p-methoxybeuzyl)-2-(pmethoxyphenyl)-7-methoxyindole-3-methanolr andZ-(p-methoxyphenyl)-3-(p methoxystyryl) 7 methoxylindole, which wereseparated as in Example 31.

EXAMPLE 45 Q-(p-MeIhOxybenZyD-Z-(p methoxyphenyl) 4iodoind0le-3-methan0l and 2-(p-meihoxyphenyl)-3 (pmeth0xyslyryl)-4-iodoindole a- (p-ethoxybenzyl) -2- (p-ethoxyphenyl-6-chloroindole- 3-methanol;

oz- (p-methoxybenzyl -2- (p-methoxyphenyl -6-fiuoroindo1e-3-methanolotp-propoxybenzyl -2- (p-propoxyphenyl -4-br0moindole-3 -methanol;

ap-methoxybenzyl -2- (p-methoxyphenyl -6-propoxyindole-3-methanol;

O6- (p-ethoxybenzyl -2- (p-ethoxyphenyl -7-methylindole- 3-methanol;

a- (p-propoxybenzyl -2- (p-propoxyphenyl -7-ethoxyindole-3-methanol;

ocp-propoxybenzyl -2- (p-propoxyphenyl -5-methylindole-3-methanol;

ap-methoxybenzyl) -2- (p-methoxyphenyl -5-bromoindole-3-methanol;

a (p-ethoxybenzyl -2- p-ethoxyphenyl) indole-3-methanol;

a- (p-methoxybcnzyl) -2- (p-methoxyphenyl -6-iodoindole-3-methanol;

2- p-ethoxyphenyl -3- (p-ethoxystyryl -6-chloroindo1e;

2- (p-methoxyphenyl) -3- (p-methoxystyryl) -6-fluoroindole;

2- p-propoxyphenyl -3- (p-propoxystyryl) -4-bromoindole 2-(p-methoxyphenyl -3 (p-methoxystyryl -6-propoxyindole;

2- (p-ethoxyphenyl -3- (p-ethoxystyryl -7-methylindole;

2- (p-propoxyphenyl -3- (p-propoxystyryl -7-ethoxyindole 2-(p-propoxyphenyl -3 (p-propoxystyryl) -5methylindole 2- p-methoxyphenyl)-3- (p-methoxystyryl -5-brornoindole;

2- (p-ethoxyphenyl -3 (p-ethoxystyryl indole;

2- (p-methoxyphenyl) -3- (p-methoxystyryl -6-iodoindole,

and the like.

EXAMPLE 46 3-(p-methoxyphenethyl)-2-(p-meth0xypheny[)ina'ole from 2-p-methoxyphenyl) -3- (p-methoxystyryl indole A solution of 0.33 g. (0.94mmole) of Z-(p-rnethoxyphenyl)-3-(p-methoxystyryl)indole was dissolvedin 200 ml. of ethanol and hydrogenated for a period of minutes in thepresence of 0.3 g. of a ten percent palladiumon-carbon catalyst, at aninitial pressure of 53 pounds of hydrogen and at a temperature ofbetween 24 and 26 C. The obtained mixture was then filtered, thefiltrate evaporated to dryness, and the thus-obtained residue wasdissolved in methylene chloride. The solution was passed through acolumn containing 16 g. of Florisil (anhydrous magnesium silicate).Elution with 30 ml. of methylene chloride gave 0.259 g. of crudematerial which was recrystallized from ether-petroleum ether to give mg.of 3 (p methoxyphenethyl) 2 (p methoxyphenyl)indole of melting point 78to 80 C. and with ultraviolet and infrared spectra in agreement with thematerial obtained in Example 16.

In the same manner given in Example 46, the styryl indoles obtained inExamples 32 through 45 can be bydrogenated in the presence of apalladium or platinum catalyst to give the3-(p-alkoxyphenethyl)-2-(p-alkoxyphenyl)indoles of Examples 17 through30.

EXAMPLE 47 2- (p-meth oxyphenyl) -3- (p-meth oxystylyl) indole Asolution of 0.373 g. (1 mmole) ofa-(p-methoxybenzyl)-2-(p-methoxyphenyl)indole-3-methanol in 25 ml. ofchloroform was prepared and the solution was allowed to stand for 1 hourat room temperature (about 25 C.). To this solution was then added 1 ml.of 2 N ethereal hydrogen chloride solution. The mixture turned brown andafter one minute showed complete absence of the starting material, u-(-methoXybenZyD-Z-(p-methoxyphenyl)indole-3-methanol. The solution wasthen evaporated to dryness, the resulting brown material was dissolvedin methylene chloride, and the solution was passed through a columncontaining 5 g. of Florisil (anhydrous magnesium silicate). The columnwas eluted with 200 ml. of methylene chloride, which was evaporated togive 0.3 g. of crude product. This was crystallized from methanol togive 0.23 g. of 2-(p-methoxyphenyl)-3-(p-rnethoxystyryl)indole ofmelting point 142 to 143 C., identical in 14 its ultraviolet andinfrared spectra with the material obtained in Example 31.

In the same manner given in Example 47, other a-(palkoxybenzyl -2-(p-alkoxyphenyl indole-3-methanols can be treated with dilute mineralacids such as hydrogen chloride, hydrogen bromide, hydrogen iodide,dilute sulfuric acid, and the like to give the corresponding2-(palkoxyphenyl)-3-(palkoxystyryl)indoles. Particular suitable startingmaterials for this reaction are the rx-(palkoxybenzyl) -2-(p-alkoxyphenyl)indole-3-methanols of Examples 32 through 45.

By reacting as in Example 1, a Z-(p-alkoxyphenyDindole with amethylmagnesium Grignard and the resulting product with ap-alkoxyphenylacetyl chloride in which the alkoxy group of thephenylacetyl chloride is different from that of the indole compound,mixed alkoxy compounds can be obtained such as p-ethoxybenzylZ-(p-methoxyphenyl)indol-3-yl ketone;

p-propoxybenzyl Z-(p-methoxyphenyl)indol-3-yl ketone;

p-methoxybenzyl 2- (p-propoxyphenyl)indol-3-yl ketone;

p-ethoxybenzyl 2- (p-propoxyphenyl) -7-chloroindol-3-y1 ketone;

p-propoxybenzyl 2-(p-methoxyphenyl)-6-chloroir1dol-3- yl ketone;

p-methoxybenzyl 2- (p-ethoxyphenyl) -4-iodoindol-3-yl ketone;

p-propoxybenzyl 2- (p-methoxyphenyl -7-methoxyindol- 3-yl ketone; andthe like.

These p-alkoxybenzyl 2-(p-alkoxyphenyl)indol-3-yl ketones, wherein thealkoxy groups are not alike, can undergo reduction as shown in Examples16 and 31 to give the corresponding 3 (p alkoxyphenethyl) 2 (palkoxyphenyl)indo1es, Oc- (p-alkoxybenzyl -2- (p-alkoxyphenyl) indole 3methanols and 2 (p-alkoxyphenyl) 3 (palkoxystyryl)indoles in which ineach compound the two alkoxy groups are unlike. Representative compoundsthus obtained include:

3 (p-ethoxyphenethyl -2- (p-methoxyphenyl indole;

3 (p-propoxyphenethyl -2- (p-methoxyphenyl indole;

3 -(p-methoxyphenethyl) -2-(p-propoxyphenyl)indo1e;

3 (p-ethoxyphenethyl) -2- (p-proproxyphenyl) -7-chloroindole;

3 p-propoxyphenethyl -2- (p-methoxyphenyl) -6-chloroindole;

3 p-methoxyphenethyl) -2- (p-ethoxyphenyl) -4-iodoindole;

3- (p-prop oxyphenethyl) -2- (p-methoxyphenyl -7-methoxyindole 3-(p-ethoxyphenethyl) -2- (p-methoxyphenyl) -5-methylindole;

oc- (p-ethoxybenzyl -2- (p-methoxyphenyl indole-B-methanol a-(p-p'ropoxybenzyl) -2- (p-methoxyphenyl) indole-3- methanol;

rx- (p-methoxybenzyl -2- (p-propoxyphenyl) indole-3- methanol;

zxp-ethoxybenzyl -2- (p-propoxyphenyl) -7-ch1oroindole- 3-methanol;

a- (p-propoxybenzyl -2- (p-methoxyphenyl) -6-chloroindole-3-methanol;

a- (p-methoxybenzyl) -2- (p-ethoxyphenyl) -4-iodoindole- 3-rnethanol a-(p-propoxybenzyl -2- (p-methoxyphenyl -7-methoxyindole-3 methanol;

oc- (p-ethoxybenzyl -2- (p-methoxyphenyl) -5-rnethy1in- Vdole-3-methanol;

2- (p-ethoxyphenyl -3- (p-methoxystyryl -indole;

2- (ppropoxyphenyl -3- (p-methoxystyryl indole;

2- (p-methoxyphenyl) -3- (p-propoxystyryl indole;

2- (p-ethoxyphenyl -3- (p-propoxystyryl) -7-chloroindole2-(p-propoxypl1enyl)-3-(p-methoxystyryl)-6-chloroindole;

2- (p-methoxyphenyl -3- (p-ethoxystyryl -4-iodoindole;

2-(p-propoxyphenyl)-3-(p-methoxystyryl)-7-methoxyindole; 2-(p-ethoxyphenyl -3- (p-methoxystyryl -5-rnethylindole; and the like.

I claim:

1. A p-alkoxybenzyl Z-(p-alkoxyphenyl)indol-3-yl ketone of the formula:

wherein R is selected from the group consisting of hydrogen, fluorine,chlorine, bromine, iodine, alkoxy having from 1 to 3 carbon atoms,inclusive, and alkyl having from 1 to 3 carbon atoms, inclusive, andwherein R is an alkyl group having from 1 to 3 carbonatoms, inelusive.

2. The compound according to claim 1,iwherein R is hydrogen and R ismethyl, and the compound is therefore p-methoxybenzyl2-(p-methoxyphenyl)indol-B-yl ketone.

3. The compound according to claim 1, wherein R is a 7-chlorosubstituent and R is methyl, and the compound is thereforep-methoxy-benzyl 2-(p-methoxyphen yl) -7-chloroindol-3 -yl ketone.

4. The compound according to claim 1, wherein R is a 7-bromo substituentand R is ethyl, and the compound is therefore p-ethoxybcnzyl2-(p-ethoxyphenyl)-7-bromoindo1-3-yl ketone.

5. A 3-(p alkoxyphenethyl)-2-(p-alkoxyphenyl)indole of the formula:.

III

wherein R is selected from the group consisting of hydrogen, fluorine,chlorine, bromine, iodine, alkoxy having from 1 to 3 car-hon atoms,inclusive, and alkyl having from 1 to 3 carbon atoms, inclusive, andwherein R is an alkyl group having from 1 to 3 carbon atoms, inclusive.

6. The compound according to claim 5, wherein R is hydrogen and R ismethyl, and the compound is therefore 3-(p-methoxyphenet-hyl) 2 (pmethoxyphenyl) indole.

7. The compound according to claim 5, wherein R is a 7-chlorosubstituent and R is methyl, and the compound is therefore3-(methoxyphenethyl)-2-(p-methoxyphenyl)-7-ehloroindole.

8. The compound according to claim 5, wherein R is a 7-bromo substituentand R is ethyl, and the compound is therefore3-(p-ethoXy-phenethyl)-2-(p ethoxyphenyl) 7-hromoindole,

1 6 9. An a-(p-alkoxybenzyl)-2-(p-alkoxyphenylfindolemethanol of theformula:

wherein R is selected from the group consisting of hydrogen, fluorine,chlorine, bromine, iodine, alkoxy having 1 to 3 carbon atoms, inclusive,and alkyl having from 1 to 3 carbon atoms, inclusive, and wherein R isan alkyl group having from 1 to 3 carbon atoms, inclusive.

10. The compound according to claim 9, wherein R is hydrogen and R ismethyl, and the compound is therefore a-(p-met-hoxybenzyl) -2-(p-methoxyphenyl) ind0le-3- methanol.

11. The compound according to claim 9, wherein R is a 7-chlorosubstituent and R is methyl, and the compound is thereforea-(p-methoxybenzyl)-2-(p-meth0xyphenyl -7-chloroindole-3 -methanol.

12. The compound according to claim 9, wherein R is a 7-bromosu-bstituent and R is ethyl, and the compound is thereforea-(p-ethoxybcnzyl)-2-(p-ethoxyphenyl) -7-bromoindole-3 -methanol.

13. A 2-(p-alkoxyphenyl)-3-(p-alkoxystyryl)indole of the formula:

-CH=CHAOR2 wherein R is selected from the group consisting of hydrogen,fluorine, chlorine, bromine, iodine, alkoxy having 1 to 3 carbon atoms,inclusive, and alkyl having from 1 to 3 carbon atoms, inclusive, andwherein R is an alkyl group having from 1 to 3 carbon atoms, inclusive.v

14, The compound according to claim 13, wherein R is hydrogen and R ismethyl, and the compound is therefore Z-(p-methoxyphenyl) 3 (pmethoxystyryl) indole.

15. The compound according to claim 13, wherein R is a 7-chlorosubstituent and R is methyl, and the compound is thereforeZ-(p-methoxyphenyl)-3-(p-methoxystyryl -7-ehloroindole.

16. The compound according to claim 13, wherein R is a 7-bromosubstituent and R is ethyl, and the compound is therefore2-(p-ethoxyphenyl)-3-(p-ethoxystyryl) 7-bromoindole.

References Cited UNITED STATES PATENTS 2,944,055 7/1960 Anthony260-326.15 2,991,291 7/1961 Szmuszkovicz 260326. 1 6 3,076,814 2/1963Specter et a1 260326.l6 3,218,333 11/1965 Roozemond 260326.15

FOREIGN PATENTS 553,622 6/1957 Belgium. 869,775 6/ 1961 Great Britain.

OTHER REFERENCES Fieser et al.: Advanced Organic Chemistry, New York,Reinhold Publishing Corp., 1961, p. 176.

ALEX MAZEL, Primary Examiner.

M. U. OBRlEN, J. A. NARCAVAGE,

Assistant Examiners,

1. A P-ALKOXYBENZYL 2-(P-ALKOXYPHENYL)INDOL-3-YL KETONE OF THE FORMULA:5. A 3-(P-ALKOXYPHENETHYL)-2-(P-ALKOXYPHENYL) INDOLE OF THE FORMULA: 9.AN A-(P-ALKOXYBENZYL)-2-(P-ALKOXYPHENYL) INDOLE-3METHANOL OF THEFORMULA:
 13. A 2-(P-ALKOXYPHENYL)-3-(P-ALKOXYSTYRYL) INDOLE OF THEFORMULA: